Overactive bladder is a pathological condition observed in patients showing symptoms such as urinary urgency or urinary frequency. Some patients with overactive bladder show urinary urge incontinence and others do not. Micturition reflex is physiologically controlled by the complex reflex pathways including peripheral and central nervous systems [Urology, Vol. 50, Supplement No. 6A, pp. 36-52 (1997)]. “Urinary urgency” refers to a sudden and strong desire to void, and “urinary urge incontinence” refers to involuntary urinary leakage associated with urinary urgency.
In patients suffering from the symptoms such as urinary urgency and urinary urge incontinence due to overactive bladder, involuntary (uninhibited) contraction of the detrusor muscle is frequently observed in a cystometric measurement, and it is called detrusor overactivity. This detrusor overactivity is considered to be a main cause of urinary urgency and also of urinary urge incontinence, and urinary urgency can lead to urinary frequency. The detrusor overactivity is called neurogenic bladder (detrusor hyperreflexia) when a neurologic problem is found in a patient, and unstable bladder (detrusor instability) when a neurologic problem is not found. Unstable bladder is considered to be due to potential neurogenic bladder or the disorder of the bladder smooth muscle per se (or both of them). Examples of neurologic problems relating to neurogenic bladder includes Parkinson's disease, stroke, diabetes, multiple sclerosis, neuropathy, spinal injury, etc.
Tricyclic compounds having the activity to prolong the intervals of bladder contractions and pharmaceutically acceptable salts thereof are known as therapeutic agents for urinary incontinence (WO97/14672 and WO98/46587). However, it is not known that the compound groups inhibit overactive bladder.